Hermans C, Aly O, Nyberg B I, Peterson C, Bernard A
Industrial Toxicology and Occupational Medicine Unit, Catholic University of Louvain, Brussels, Belgium.
Clin Chim Acta. 1998 Apr 27;272(2):101-10. doi: 10.1016/s0009-8981(98)00006-0.
Clara cell protein (CC16) is a 16 kiloDalton protein secreted by Clara cells in the lining fluid of bronchiolar and bronchial epithelium. Recently, Nomori et al., using a nephelometric latex immunoassay, reported a strong correlation between serum CC16 (sCC16) and serum lipids as well as the body mass index (BMI) [Nomori H, Horio H, Takagi M Kobayashi Y, Hirabayashi Y. Clara cell protein correlation with hyperlipidemia. Chest 1996;110:680-4]. The same authors found higher values of sCC16 in males compared to females and did not detect any significant influence of tobacco smoking. Since these results are in disagreement with previous observations showing consistently a decrease of sCC16 in smokers and no influence of sex, we have reassessed in healthy subjects the determinants of sCC16 using two different assays: a particle counting-based latex immunoassay (LIA) using polyclonal antibodies and a fluorescence enzyme immunoassay (FEIA) using monoclonal antibodies. sCC16 was determined in a group of 52 female and 44 male healthy subjects (age 18 to 66 years), including 35 smokers and 61 nonsmokers. sCC16 measured by LIA and FEIA were well correlated (r = 0.92, n = 96, P < 0.0001) with values (geometric mean and range) of 13.3 (5.2-34.5) and 14.7 (4.1-53.1) microg/l, respectively. The determinants of sCC16 measured by both techniques were traced by stepwise regression analysis using as independent variables age, sex, smoking status, BMI or serum lipids (total cholesterol and triglycerides) and the glomerular filtration rate (GFR) estimated on the basis of serum creatinine or beta2-microglobulin. Only two significant determinants emerged: tobacco smoking which correlated negatively and the GFR which correlated positively with sCC16. No influence of serum lipids, BMI, age and sex on sCC16 was detected. We think that an analytical interference with serum lipids explains the results by Nomori et al. which are not confirmed here by two independent techniques and are inconsistent with the current understanding of the physiopathology of the Clara cell and its main secretory product, CC16.
克拉拉细胞蛋白(CC16)是一种由细支气管和支气管上皮衬液中的克拉拉细胞分泌的16千道尔顿蛋白。最近,野守等人使用散射比浊乳胶免疫测定法,报告血清CC16(sCC16)与血脂以及体重指数(BMI)之间存在强相关性[野守H,堀尾H,高木M,小林Y,平林Y。克拉拉细胞蛋白与高脂血症的相关性。《胸部》1996年;110:680 - 4]。同一组作者发现男性的sCC16值高于女性,且未检测到吸烟有任何显著影响。由于这些结果与先前的观察结果不一致,先前的观察结果一直显示吸烟者的sCC16降低且不受性别影响,我们使用两种不同的测定方法在健康受试者中重新评估了sCC16的决定因素:一种使用多克隆抗体的基于颗粒计数的乳胶免疫测定法(LIA)和一种使用单克隆抗体的荧光酶免疫测定法(FEIA)。在一组52名女性和44名男性健康受试者(年龄18至66岁)中测定了sCC16,其中包括35名吸烟者和61名非吸烟者。通过LIA和FEIA测定的sCC16与各自的值(几何平均值和范围)相关性良好(r = 0.92,n = 96,P < 0.0001),LIA测定值为13.3(5.2 - 34.5)μg/l,FEIA测定值为14.7(4.1 - 53.1)μg/l。使用年龄、性别、吸烟状况、BMI或血脂(总胆固醇和甘油三酯)以及根据血清肌酐或β2 - 微球蛋白估算的肾小球滤过率(GFR)作为自变量,通过逐步回归分析追踪两种技术测定的sCC16的决定因素。仅出现两个显著的决定因素:吸烟与sCC16呈负相关,GFR与sCC16呈正相关。未检测到血脂、BMI、年龄和性别对sCC16有影响。我们认为对血脂的分析干扰解释了野守等人的结果,这里两种独立技术未证实这些结果,且这些结果与目前对克拉拉细胞及其主要分泌产物CC16的生理病理学的理解不一致。